1. Technical Field
This invention pertains to pharmaceutical tablet formulations. More particularly this invention pertains to tablets containing salsalate. In another aspect, this invention pertains to masking taste and esophageal irritation caused by pharmaceutical formulations, particularly tablets.
2. Description of the Related Art
Salsalate (salicylsalicylic acid; 2-hydroxybenzoic acid 2-carboxyphenyl ester) is a nonsteroidal anti-inflammatory drug (NSAID). Salsalate has a very unpleasant taste and causes irritation of the mucous membranes of the esophagus. Known salsalate tablets overcome this problem by either film coating or by including excipients in an amount great enough to mask the taste and irritation. For example, DISALCID.RTM. (commercially available from Riker Laboratories, Inc., St. Paul, Minn.) is supplied as a tablet coated with hydroxypropyl methylcellulose and additionally containing magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, starch, talc, and dye. Physicians Desk Reference, 1988, 42, 1678.
Salsalate is generally non-compressible and shows a wide variety of tableting characteristics depending on the method of manufacture. Salsalate tablets can be difficult to compress and may be subject to internal lamination, which may lead to a catastrophic tablet failure known as capping. Capping and its relation to axial and radial tensile strength are discussed in Acta Pharm. Suecica, 1984, 21, 1. Hydroxypropyl cellulose is a known pharmaceutic aid. It has been used as a binder, a film former, and as a granulating agent in both conventional and sustained release formulations. The use of hydroxypropyl cellulose in salsalate formulations is known. For example, U.S. Pat. No. 4,666,716 discloses an anti-diarrheal composition containing an NSAID such as salsalate and a polymeric hydroabsorptive agent in a ratio of between about 1:30 and about 1:600. The composition can be in the form of a tablet containing a binder such as hydroxypropyl cellulose. It is notable that these compositions contain the NSAID as a relatively minor component (i.e., at most several percent of the total weight of the composition).
U.S. Pat. No. 4,789,667 discloses pharmaceutical compositions comprising an effective amount of drug and an effective amount of a pyroglutamate as a skin-penetration enhancer. A variety of drugs, presentations, and excipients are disclosed. The composition can be in the form of a tablet, the drug can be an anti-inflammatory agent such as salsalate, and excipients in a tablet can include hydroxypropyl cellulose. The amounts of drug and excipient in a tablet are not addressed.